{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:50:01Z","timestamp":1792133401912,"version":"4.4.0"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"4","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,8,1]]},"abstract":"<jats:p>A family of insulin receptor substrate (IRS) proteins mediates the pleiotropic effects of insulin and insulin-like growth factor 1 (IGF-1) on cellular function by recruiting several intracellular signalling networks. Conventional murine knockout strategies have started to reveal distinct physiological roles for the IRS proteins. Deletion of Irsl produces a mild metabolic phenotype with compensated insulin resistance but also causes marked growth retardation. In contrast, mice lacking IRS-2 display nearly normal growth but develop diabetes owing to a combination of peripheral insulin resistance and \u03b2-cell failure. As well as the classical metabolic events regulated by insulin signalling pathways, studies in lower organisms have implicated insulin\/IGF-1 signalling pathways in the control of food intake and reproductive function. Our analysis of IRS-2 knockout mice shows that female mice are infertile owing to defects in the hypothalamus, pituitary and gonad. IRS-2\u22121 mice have small, anovulatory ovaries with reduced numbers of follicles. Levels of the pituitary hormones luteinizing hormone and prolactin and gonadal steroids are low in these animals. Pituitaries of IRS-2\u22121 animals are decreased in size and contain reduced numbers of gonadotrophs. Additionally, IRS-2\u22121 females display increased food intake and develop obesity, despite elevated leptin levels, suggesting abnormalities in hypothalamic function. Coupled with recent observations that brain-specific deletion of the insulin receptor causes a similar phenotype, these findings implicate IRS signalling pathways in the neuroendocrine regulation of reproduction and energy homeostasis.<\/jats:p>","DOI":"10.1042\/bst0290525","type":"journal-article","created":{"date-parts":[[2005,1,31]],"date-time":"2005-01-31T12:49:28Z","timestamp":1107175768000},"page":"525-529","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Insulin receptor substrate proteins and neuroendocrine function"],"prefix":"10.1042","volume":"29","author":[{"given":"D. J.","family":"Withers","sequence":"first","affiliation":[{"name":"Department of Metabolic Medicine, ICSM Hammersmith Campus, Du Cane Road, London W12 0NN, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Society Transactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/29\/4\/525\/528845\/bst0290525.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/29\/4\/525\/528845\/bst0290525.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T19:52:50Z","timestamp":1637178770000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article\/29\/4\/525\/62927\/Insulin-receptor-substrate-proteins-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,8,1]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2001,8,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bst0290525","relation":{},"ISSN":["0300-5127","1470-8752"],"issn-type":[{"value":"0300-5127","type":"print"},{"value":"1470-8752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,8,1]]}}}